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Screening for pre-eclampsia in the first trimester of pregnancy

Pictogramme horloge Corinne Sault Pictogramme horloge February 2015

Pre-eclampsia (PE) is a disease with a multifactorial aetiology. In France, this condition affects approximately 24,000 patients and 800,000 pregnancies per year, which represents 1% to 3% of first pregnancies and 0.5% to 1.5% of subsequent pregnancies (Goffinet, 2010). The associated maternal and foetal morbi-mortality is high: it is the second cause of maternal death in France, after bleeding on delivery, and a major cause of intrauterine growth restriction (IUGR). It is also the cause of one in three very premature births. Furthermore, PE causes long-term complications: women who have had pre-eclampsia have a greatly increased risk of cardiovascular morbi-mortality.

The definition of PE is essentially clinical: systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg combined with proteinuria >0.3 g/24h occurring after 20 weeks of pregnancy; the presence of oedema is classical but not discriminatory. PE develops as of the first trimester of pregnancy, but symptoms only appear in the third trimester. The complications of PE are:

  • Maternal: severe increase in blood pressure requiring termination of the pregnancy, HELLP syndrome, eclampsia, retroplacentary haematoma, acute kidney failure, etc.
  • Foetal: IUGR, intrauterine foetal death (IUFD), prematurity, etc.

About half of PE cases present before 34 weeks of amenorrhoea, and are termed early PE; the other half, after 34 weeks, are termed late PE. Early PE is more worrying as it is associated with iatrogenic prematurity or serious foetal retardation.

Screening for PE is a risk calculation taking account of the risk factors identified by interview and clinical examination, biophysical measurements (first-trimester ultrasound scan with measurement of craniocaudal length, blood pressure and pulsatility index in the uterine arteries by Doppler ultrasound) and biological markers (PAPP-A and PGF). The serum concentrations of PGF also allow the risk of isolated IUGR to be estimated and ultrasound monitoring to be adapted to better target the patients at risk. Undiagnosed IUGR represents the most common cause of avoidable intrauterine foetal death (Roux-Terrier et al, 2014).

The interest of early screening for PE is the possibility of introducing aspirin prophylaxis. Bujold et al. (2014) have shown that aspirin only has an effective preventative effect on pre-eclampsia when treatment is commenced before the 16th week of pregnancy.

Calculation of the risk of pre-eclampsia

The risk is calculated in the laboratory by calculation software adapted to the reagents and operating on the same principle as the software for calculation of the risk of Down syndrome. Clinical, biophysical and biological risk factors have been established from a cohort of pregnant women, some of whom developed pre-eclampsia and others who did not.

Clinical information taken into account in the calculation:
  • BMI: obesity is a risk factor for PE;
  • Geographical origin: the risk of PE is increased in women of sub-Saharan African or Caribbean origin;
  • Parity: a first pregnancy is a risk factor for PE;
  •  Personal or family history of PE;
  • Chronic high blood pressure (treated or not);
  • Smoking: smoking reduces the risk of PE
Biophysical measurements:
  • Blood pressure: measured between 11+0 and 13+6 weeks, ideally on both arms (otherwise on a single arm), enabling the calculation of the mean arterial pressure (MAP) from the systolic and diastolic pressures. The MAP has a positive predictive value for pre-eclampsia that is higher than that of a simple measurement of arterial pressure (Poon et al, 2012). The calculation is carried out by the software, and then expressed as MoM (multiples of the median) taking account of the patient’s weight.
  • Doppler ultrasound of the uterine arteries: pulsatility index (PI).
Biochemical marker:
  • PAPP-A (Pregnancy-Associated Plasma Protein A): metalloproteinase playing an important role in trophoblastic invasion. It is also a maternal serum marker for the calculated combined risk of foetal Down syndrome. A low serum concentration of PAPP-A implies a risk of Down syndrome, Edwards syndrome, pre-eclampsia, IUGR and/or spontaneous miscarriage (low PAPP-A and hCGß).
  • PGF (Placental Growth Factor), produced by the placenta, is an angiogenesis mediator belonging to the family of vascular endothelial growth factors (VEGF). The serum concentration of PGF is lower in patients who will develop pre-eclampsia than in unaffected patients. It could also be of interest to predict vascular IUGR and possibly prematurity.

The measurements are carried out on a blood sample taken between 11+0 and 13+6 weeks (as for the combined screening in the first trimester for foetal Down syndrome).

The performance is better for the screening for early PE (the more “worrying”). The combination of serum measurements and clinical information enables 93% of early PE to be detected (with about 5% false positives); by adding biophysical markers, the detection rate is 96.3% (Akolekar et al, 2013).



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